WR-1065, THE ACTIVE METABOLITE OF AMIFOSTINE (ETHYOL(R)), DOES NOT INHIBIT THE CYTOTOXIC EFFECTS OF A BROAD RANGE OF STANDARD ANTICANCER DRUGS AGAINST HUMAN OVARIAN AND BREAST-CANCER CELLS

Amifostine (WR-2721, Ethyol(R)), a phosphorylated thiol, demonstrates the unique ability to protect normal but not tumour tissue from cytoto xic damage induced by radiation therapy and chemotherapy. This study t ested the effect of amifostine's active metabolite, the free thiol, WR -1065, on the cytotoxicity of standard anticancer drugs against human A2780 ovarian and MCF7 breast cancer cell lines in vitro, using the we ll-characterised sulphorhodamine B assay. 50% inhibitory concentration (IC50) values were determined for each of 16 different anticancer dru gs in the presence and absence of the highest nontoxic dose of WR-1065 from concentration-response curves constructed in triplicate and base d on 18 replicate cell culture plates for each tested drug concentrati on. Pretreatment with WR-1065 had no statistically significant effect on the IC50 value of any of the 16 drugs tested against either the A27 80 or MCF7 human tumour cells. These data expand upon previous reports showing that amifostine does not protect tumours from the cytotoxic e ffects of anticancer agents. The ability of amifostine to protect agai nst dose-limiting toxicity to a variety of normal tissues without prot ection of tumour should enhance the efficacy ratio of a wide range of standard anticancer drugs. Copyright (C) 1996 Elsevier Science Ltd